text: Currently there are six known structural families.  Their conserved structural motifs are:
  * LAGLIDADG: Every polypeptide has 1 or 2 LAGLIDADG motifs. The sequence LAGLIDADG is a conserved sequence of amino acids where each letter is a code that identifies a specific residue. This sequence is directly involved in the DNA cutting process. Those enzymes that have only one motif work as homodimers, creating a saddle that interacts with the major groove of each DNA half-site. The LAGLIDADG motifs contribute amino acid residues to both the protein-protein interface between protein domains or subunits, and to the enzyme's active sites. Enzymes that possess two motifs in a single protein chain act as monomers, creating the saddle in a similar way.  The first structures to be determined of homing endonucleases (of PI-SceI and I-CreI, both reported in 1997) were both from the LAGLIDADG structural family.,  The following year, the first structure of a homing endonuclease (I-CreI) bound to its DNA target site was also reported.
  * GIY-YIG: These have only one GIY-YIG motif, in the N-terminal region, that interacts with the DNA in the cutting site. The prototypic enzyme of this family is I-TevI which acts as a monomer.  Separate structural studies have been reported of the DNA-binding and catalytic domains of I-TevI, the former bound to its DNA target and the latter in the absence of DNA.
  * His-Cys box (): These enzymes possess a region of 30 amino acids that includes 5 conserved residues: two histidines and three cysteins. They co-ordinate the metal cation needed for catalysis. I-PpoI is the best characterized enzyme of this family and acts as a homodimer.  Its structure was reported in 1998. It is possibly related to the H-N-H family, as they share common features.
  * H-N-H:  (): These have a consensus sequence of approximately 30 amino acids. It includes two pairs of conserved histidines and one asparagine that create a zinc finger domain.  I-HmuI () is the best characterized enzyme of this family, and acts as a monomer.  Its structure was reported in 2004 ().
  * PD-(D/E)xK (): These enzymes contain a canonical nuclease catalytic domain typically found in type II restriction endonucleases.  The best characterized enzyme in this family, I-Ssp6803I (), acts as a tetramer.  Its structure was reported in 2007 (). The overall fold is conserved in many endonuclease families, all of which belong to the PD-(D/E)xK superfamily.
  * Vsr-like/EDxHD (DUF559, ): These enzymes were discovered in the Global Ocean Sampling Metagenomic Database and first described in 2009. The term Vsr-like refers to the presence of a C-terminal nuclease domain that displays recognizable homology to bacterial Very short patch repair (Vsr) endonucleases. The structure has been solved in 2011, confirming the Vsr homology. Is considered part of the PD-(D/E)xk superfamily.